Oxidative Stress Survival in a Clinical Saccharomyces cerevisiae Isolate Is Influenced by a Major Quantitative Trait Nucleotide
Oxidative Stress Survival in a Clinical Saccharomyces cerevisiae Isolate Is Influenced by a Major Quantitative Trait Nucleotide
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DOI：
10.1534/genetics.111.128256
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发表时间：
2011-07-01
期刊：
影响因子：
3.3
通讯作者：
Dietrich, Fred S.
中科院分区：
文献类型：
--
作者：
Diezmann, Stephanie;Dietrich, Fred S.
表征真核生物遗传多样性的主要挑战之一是作为多个等位基因的累积效应的表型的作图。我们研究了酵母酿酒酵母的氧化应激耐受性，这是一种在群体中表现出表型变异的性状。最初的杂交表明这是一个数量性状。微生物在许多环境中经历氧化应激，包括在高等真核生物感染期间。氧化应激耐受性的自然变异是人体免疫系统对氧化应激反应的一个重要方面，也是微生物病原体的一个重要特征。一种临床分离的通常为良性的酵母菌S。发现酿酒酵母比实验室菌株在氧化应激下存活得明显更好。我们研究了通过杂交这些菌株，表型1500分离子，和基因分型的高存活率的分离子的基因基础增加过氧化物生存的散装和单分离子DNA微阵列杂交。这一努力导致了转录因子Rds2的等位基因的鉴定，其有助于应激反应。Rds2以前没有与氧化应激的生存相关。它在氧化应激反应中的作用的鉴定是一个特定性状的例子，似乎是有益的酿酒酵母作为病原体生长时。了解这种真菌特异性转录因子在致病性中的作用对于解释真菌如何感染和定植人类宿主非常重要，并可能最终导致新的药物靶点。
One of the major challenges in characterizing eukaryotic genetic diversity is the mapping of phenotypes that are the cumulative effect of multiple alleles. We have investigated tolerance of oxidative stress in the yeast Saccharomyces cerevisiae, a trait showing phenotypic variation in the population. Initial crosses identified that this is a quantitative trait. Microorganisms experience oxidative stress in many environments, including during infection of higher eukaryotes. Natural variation in oxidative stress tolerance is an important aspect of response to oxidative stress exerted by the human immune system and an important trait in microbial pathogens. A clinical isolate of the usually benign yeast S. cerevisiae was found to survive oxidative stress significantly better than the laboratory strain. We investigated the genetic basis of increased peroxide survival by crossing those strains, phenotyping 1500 segregants, and genotyping of high-survival segregants by hybridization of bulk and single segregant DNA to microarrays. This effort has led to the identification of an allele of the transcription factor Rds2 as contributing to stress response. Rds2 has not previously been associated with the survival of oxidative stress. The identification of its role in the oxidative stress response here is an example of a specific trait that appears to be beneficial to Saccharomyces cerevisiae when growing as a pathogen. Understanding the role of this fungal-specific transcription factor in pathogenicity will be important in deciphering how fungi infect and colonize the human host and could eventually lead to a novel drug target.